This invention relates to the induction of cellular lethality in cancer cells, in particular cancer cells that are deficient in homologous recombination (HR) dependent DNA double strand break (DSB) repair.
The effective repair of DNA damage in cells relies on mechanisms of damage sensing followed by the transduction of damage signals to downstream effectors that arrest at cell cycle checkpoints and repair DNA damage. Cells contain a number of distinct pathways of signals and effectors that mediate the repair of different types of DNA damage. These pathways include base excision repair (BER), homologous recombination (HR) dependent DNA double strand break (DSB) repair, non-homologous end joining (NHEJ), nucleotide excision repair (NER), base excision repair (BER) and mismatch repair (MMR). The interaction and interdependence between the various DNA repair pathways remains poorly understood.